A high-throughput screen for mitochondrial function reveals known and novel mitochondrial toxicants in a library of environmental agents

Mitochondrion. 2016 Nov;31:79-83. doi: 10.1016/j.mito.2016.10.001. Epub 2016 Oct 4.

Abstract

Mitochondrial toxicity is emerging as a major mechanism underlying serious human health consequences. This work performs a high-throughput screen (HTS) of 176 environmental chemicals for mitochondrial toxicity utilizing a previously reported biosensor platform. This established HTS confirmed known mitochondrial toxins and identified novel mitotochondrial uncouplers such as 2, 2'-Methylenebis(4-chlorophenol) and pentachlorophenol. It also identified a mitochondrial 'structure activity relationship' (SAR) in the sense that multiple environmental chlorophenols are mitochondrial inhibitors and uncouplers. This study demonstrates proof-of-concept that a mitochondrial HTS assay detects known and novel environmental mitotoxicants, and could be used to quickly evaluate human health risks from mitotoxicants in the environment.

Keywords: Bioenergetics; Biosensor; Cell-based assay; Environmental chemicals; High-throughput screening; Mitochondria; Oxygen; Toxicants.

MeSH terms

  • Biosensing Techniques / methods*
  • Cell Line
  • Energy Metabolism / drug effects
  • Environmental Pollutants / toxicity*
  • Epithelial Cells / drug effects
  • Epithelial Cells / physiology
  • High-Throughput Screening Assays / methods*
  • Humans
  • Mitochondria / drug effects*
  • Mitochondria / metabolism*
  • Neurons / drug effects
  • Neurons / physiology
  • Toxicology / methods*
  • Uncoupling Agents / toxicity

Substances

  • Environmental Pollutants
  • Uncoupling Agents